Trends in colorectal cancer screening compliance and incidence among 60‐ to 74‐year‐olds in China

Abstract Background Compliance with colonoscopy among elderly individuals participating in colorectal cancer (CRC) screening programs is unsatisfactory, despite a high detection rate of bowel‐related diseases. In this study, our aim was to analyze the impact of risk factors on the trends of compliance and detection rates in colonoscopy among high‐risk individuals aged 60–74. Methods A retrospective study was conducted on the high‐risk individuals aged 60–74 participating in the 2021 CRC screening program in Tianjin, China. Logistic regression analyses, including both univariate and multivariate analyses, were performed to explore the impact of different risk factors on colonoscopy compliance among the high‐risk individuals. Besides, the study investigated the influence of various risk factors on the detection rates of bowel‐related diseases among the high‐risk individuals who underwent colonoscopy. Results A total of 24,064 high‐risk individuals were included, and 5478 individuals received a free colonoscopy, with an overall compliance of 22.76%. Among them, the adenoma detection rate was 55.46%. Males and individuals with a positive FIT had high compliance and detection rates for CRC, advanced adenomas (AA), advanced colorectal neoplasia (ACN), and colorectal neoplasm (CN). Individuals aged 70–74 were associated with low compliance but high CRC, ACN, and CN detection rates. Individuals who reported a history of chronic constipation, bloody mucous, and CRC in first‐degree relative showed high compliance but no significantwere associated with the detection rates of CRC, AA, and CN. Conclusion This study reported several risk factors associated with the screening behaviors for CRC. Patterns and trends in CRC, AA, ACN, and CN compliance and detection rates correlate with risk factors.


| INTRODUCTION
The incidence and mortality of colorectal cancer (CRC) have witnessed a significant increase, and this trend is also evident in China. 1,2Specifically, in China, incidence (average annual percentage change (AAPC) 1.6, 95% CI 1.3-1.9)and mortality (AAPC 1.3, 95% CI 0.9-1.7)are increasing rapidly in males; the trend in female mortality is slightly increasing (AAPC 0.6, 95% CI 0.0-1.2) and incidence is stable. 2CRC screening could be used as an effective tool to reduce the incidence rate and mortality of CRC. 3,4Regrettably, there are still significant differences in CRC screening strategies and performances.
Colonoscopy plays a significant role in CRC screening. 5][8][9][10][11][12] Inadequate compliance with colonoscopy is affected by many factors, such as the invasiveness of colonoscopy, the requirements of intestinal preparation, and insufficient awareness of CRC screening.In addition, regional and ethnic differences may also be the influencing factors. 13,14Therefore, it is critical to try to improve compliance by implementing a variety of programs. 157][18] The screening program in china that combines high-risk factor questionnaire (HRFQ) with fecal immunochemical test (FIT) 19 and subsequent colonoscopy is also a combined strategy.Despite the widespread application of this CRC screening program, there is still not enough evidence regarding its effectiveness and convenience.Therefore, there is a need to analyze the compliance and detection rate trends of the relevant risk factors in this program.
It has been previously found that colonoscopy compliance declines 20 with age, while the incidence rate of bowel-related diseases such as CRC increases with age.Consequently, it is critical in the screening process to weigh and recommend whether the elderly high-risk populations should undergo colonoscopy.A retrospective study of CRC screening data in Tianjin, China, including participants aged 60-74 years in 2021, was conducted in the current study.The differences in colonoscopy compliance among different high-risk groups were analyzed.Additionally, the value of various high-risk factors in detecting bowel-related diseases among high-risk populations undergoing colonoscopy was investigated.This work aims at providing some basis for optimizing CRC screening strategies.

| Study design and populations
A screening program combining HRFQ and FIT tests was launched in Tianjin, China in 2012. 21The screening program is open to all individuals within the specified age group.Individuals will undergo both HRFQ and FIT tests, and if either test yields a positive result, they will be identified as highrisk individuals and offered a free colonoscopy examination.
The recommended positive definition of HRFQ is considered to meet any of the following criteria: (1) a history of CRC in a first-degree relative; (2) a history of cancer or intestinal polyps; (3) individuals with two or more of the following: a history of chronic constipation, a history of chronic diarrhea, a history of bloody mucous stools, adverse life events (e.g., divorce and death of a close relative), a history of chronic appendicitis or appendectomy, and a history of chronic cholecystitis or gallstones.And a positive HRFQ result indicates an increased risk of CRC.][24][25][26][27] In 2021, the primary populations screened were those aged 60-74.Our study included a total of 24,064 high-risk individuals, with exclusion criteria applied to those outside the specified age group, those with missing data, and those who had previously undergone primary screening.Figure 1 illustrates the flow chart depicting the inclusion and arrangement of the individuals.

| Risk factors and demographic characteristics
All variables in the HRFQ and FIT were considered risk factors for this study.In addition, the database also recorded demographic characteristics such as gender, age, education level, occupation, and region of the populations recruited in the screening.

| Colonoscopy and results evaluation
Colonoscopy was carried out by qualified hospitals in Tianjin.All the endoscopists involved in the screening program had extensive experience in colonoscopy.A thorough inspection was performed following the standard inspection process, and excision or biopsy was performed as needed.Endoscopic and histopathological data from colonoscopy were accurately recorded and entered into the database by the staff.Colorectal neoplasia (CN) was defined as CRC or AA or polyp; advanced colorectal neoplasia (ACN) was defined as CRC or AA; and AA was characterized as an adenoma that measured at least 1 cm in diameter, or a villous adenoma (with at least 25% villous component) or adenoma with high-grade dysplasia.Hyperplastic polyps were not included in the definition of polyps in our study.Adenoma detection rate (ADR) was defined as the proportion of patients undergoing colonoscopy in whom at least one adenoma was detected.

| Statistical analysis
A descriptive analysis was employed to describe the study's demographic characteristics and clinical factors.The method of univariate and multivariate logistic regression was used to analyze (1) the impact of different risk factors on the colonoscopy compliance among high-risk individuals, and (2) the impact of different risk factors on the detection rate of CRC, AA, ACN, and CN in the highrisk individuals.
Furthermore, in addition to our main analysis, we conducted an analysis using instrumental variables (IV).9][30][31][32] To tackle endogeneity issues in regression analysis, we utilized probit models and the IV probit tool for comparison, enabling the estimation of the screening effect in the presence of unmeasured hidden confounders.The corresponding odds ratios (ORs) and confidence intervals (CIs) with 95% confidence were calculated for each independent risk factor.A p-value <0.05 was statistically significant.All statistical analyses were conducted using R software (Version 4.1.2) and stata (Version 14).

| Demographic characteristics and risk factors of high-risk groups
In the Tianjin CRC Screening Project 2021, a total of 24,064 high-risk individuals aged 60-74 underwent screening.However, only 5478 high-risk individuals underwent colonoscopy examinations, resulting in an overall compliance rate of 22.76% (Figure 1).Among the 5478 individuals, 811 individuals (14.80%) tested positive on the HRFQ but did not undergo FIT testing, 957 individuals   Male and individuals with a positive FIT were associated with high compliance rates and high CRC, AA, ACN, and CN detection rates (Tables S1-S5; Figure 2; Figure S1).
3.2.2| Factors with low compliance and high detection rates Individuals aged 70-74 was associated with low compliance rate but high CRC, ACN, and CN detection rates (Tables S1,S2,S4 and S5; Figure 2; Figure S1).

| Factors with low compliance and detection rates
Elementary School/below, history of chronic appendicitis or appendectomy, chronic cholecystitis or gallstones, and adverse life events were associated with low compliance rates but not associated with CRC, AA, ACN, or CN detection rates (Tables S1-S5; Figure 2; Figure S1).Agriculturerelated area was associated with low compliance rate and low CRC, AA, and ACN detection rates (Tables S1-S4; Figure 2; Figure S1).Chronic diarrhea was not associated with compliance rate but with low AA and CN detection rates (Tables S1,S3 and S5; Figure 2; Figure S1).

| Factors with high compliance and low detection rates
History of mucus blood stool, history of CRC in a firstdegree relative were associated with high compliance rates but not associated with CRC, AA, ACN, or CN detection rates (Tables S1-S5; Figure 2; Figure S1).A similar trend was found for history of chronic constipation.A history of intestinal polyps was associated with high compliance rates and low CRC, AA, and ACN detection rates, but it

T A B L E 1 (Continued)
was not associated with the CN detection rate (Tables S1-S5; Figure 2; Figure S1).

| Detection of intestinal tumor diseases by colonoscopy
The number of colonoscopies needed to detect one case of CRC, AA, ACN, and CN was calculated to be 29.41,8.25, 6.44, and 1.70, respectively.CRC, AA, ACN, and CN were detected in 34, 121.2, 155.2, and 588.5 individuals of every 10,000 participants who underwent colonoscopy, respectively (Table 2).

| Instrumental variable analyses
Using AA, CRC, and ACN as outcome variables, the results of the first stage estimation of the iv-2sls model showed that the p-values were all significant at the 1% level and  the F-statistics were all well above the empirical value of 10 (Table S8).This suggests that the instrumental variable residential area is correlated with the explanatory variable (education).Also, the p-values of the AR and Wald exogeneity tests are all significant at the 1% level, indicating that the instrumental variable chosen for this paper is not a weak instrumental variable (Table S10).
The results of the IV probit models are consistent with the majority of the key results from logistic regression.There are only a few results that show some inconsistencies.Specifically, the results showed that individuals with an elementary school/below was associated with high CRC, AA, and ACN detection rates (Table S9-S11).Additionally, history of mucus blood stool was associated with high CRC detection rate (Table S10).Seventy to 74 years was associated with a high AA detection rate (Table S9).However, chronic diarrhea was not associated with the AA detection rate (Table S9).These findings indicate that the conclusions are reliable.

| DISCUSSION
Among the 5478 high-risk individuals, the detection rates were 3.4% for CRC, 12.12% for AA, 58.85% for CN, and the ADR was 55.46%.Although the detection rate of this study is higher than other previous studies, 20,23 the compliance is still not particularly ideal, at 22.7%.It was observed that individuals aged 70-74 had a higher disease detection rate but a lower compliance.Therefore, we conducted an additional analysis to examine the influence of risk factors on compliance and detection rates in colonoscopy examinations.
It is worth noting that a positive FIT result was found to be associated with higher compliance and detection rates, which aligns with the findings of previous research studies. 6In addition, although some studies have suggested an association between chronic constipation and CRC, 33,34 there are also numerous inconsistent conclusions. 35,36Our study found that history of chronic constipation is not associated with a higher detection rate of CRC.
The history of mucus blood stool and chronic diarrhea was also found to have similar findings.8][39] However, due to the ambiguity of mucus blood, relying solely on visual examination of the screening populations to determine the presence of blood in stool may be insufficient.This conclusion was further supported by subgroup analysis (Table S6).1][42][43] And subgroup analysis demonstrated that among individuals with a history of chronic diarrhea, the detection rate of AA and CRC was higher in those with a positive FIT compared to those with a negative FIT (Table S7).This finding aligns with the conclusions of other researchers.A similar trend was observed in the history of appendicitis surgery and gallbladder disease or gallbladder surgery.5][46] Considering the bias induced by lag time, 47 the above correlation was not significant. 46,48onsidering that doctors often recommend regular colonoscopies for high-risk individuals with colon polyps, and individuals with a history of CRC in a firstdegree relative have higher awareness of CRC, their screening compliance is better.Therefore, although a history of colon polyps and history of CRC in a firstdegree relative are important risk factors for CRC, 49 they are not independent risk factors for CRC in this study.Equally, due to their surgical or cancer history, patients have actively or passively undergone more examinations, and some of these examinations may be routine for these diseases, such as FIT, abdominal CT, and even tumor markers.This has also provided these individuals with more opportunities to detect hidden diseases, including colorectal diseases.This proactive approach to medical intervention may contribute to a reduced incidence of intestinal polyps or CRC in this particular group, suggesting a protective factor.The presence of symptoms and personal illness history indicates that increased health awareness could enhance compliance, although its predictive value for CRC or precancerous polyps is limited. 50,51e need to pay attention to the significant changes in people's health care-seeking behavior, disease prevention awareness, and medical conditions as the economy and society develop.These changes have had a certain impact on the determination of relevant risk factors in the HRFQ.To the best of our knowledge, there is a limited amount of research on the impact of different high-risk factors on compliance with colonoscopy and the detection rates of colorectal neoplastic diseases specifically within the context of the HRFQ screening strategy.Our study provides some data support for optimizing HRFQ and offers valuable evidence for decision-making.

| LIMITATIONS
Some strengths and limitations should be considered when interpreting our results.First, our data came from a large population-based CRC screening program in China, which is a significant advantage.Furthermore, strict standards were adopted to ensure the quality of the research data.Our data were obtained from a single geographic region and cannot represent the general Chinese population.So, selection bias cannot be ruled out.Second, although the sample size was large, the compliance of colonoscopy was insufficient, and there may be deviations.Third, clinical information has not been fully obtained yet, because the follow-up of the patients diagnosed with CRC is still in progress.Therefore, tumor stage information was not reported in our study.Finally, several factors of screening compliance were not captured: the local culture (e.g., religious beliefs), the geographical distance from home to the screening site, and others, could have an effect on participants' behavior toward CRC screening; which could be further explored in future studies.

| CONCLUSIONS
This study reported several risk factors associated with the screening behaviors for CRC.Patterns and trends in CRC, AA, ACN, and CN compliance and detection rates correlate with risk factors.

F I G U R E 1
Study population screening flow chart.T A B L E 1 Demographic characteristics and risk factors of high-risk groups.

3. 2 |
The impact of risk factors on the trends of compliance and detection rates in colonoscopy among high-risk individuals 3.2.1 | Factors with high compliance and high detection rates

F I G U R E 2
Odds ratio (OR) of risk factors associated with advanced colorectal neoplasia/colorectal neoplasm (ACN/CN) and colonoscopy compliance.T A B L E 2 Detection of intestinal tumor diseases detected by colonoscopy, (n,%).